The objective of the proposed work is to define the role which cyclic nucleotides play in regulating DNA synthesis and cell division during adaptive heart groth. Cyclic AMP and/or cyclic GMP are known to regulate DNA synthesis in a variety of mammalian tissues and cells. Cyclic AMP has been implicated in the control of cell differentiation in the developing heart; however, the involvement of cyclic nucleotides in regulating heart cell division during adaptive heart growth has not been examined. Aortic constriction will be used to creat comparable degrees of pressure overload and cardiac enlargement in neonatal and adult rats. In neonates, cardiac enlargement is accompanied by mitotic division of muscle as well as nonmuscle cells. Cardiac enlargement in the adult heart results from growth of pre-existing muscle cells which is accompanied by mitotic division of nonmuscle cells. Nucleotide cyclase (adenylate cyclase and gyanylate cyclase) activities and cyclic nucleotide (cAMP and cGMP) levels will be determined in heart tissue from neonatal and adult animals undergoing cardiac enlargement. Similar determinations will be made in isolated cardiac muscle and nonmuscle cells and nuclei isolated from homogenous heart cell population. Pharmacological interventions will then be employed to alter cardiac tissue cyclic nucleotide levels. By determining the activity dividing cell population(s) in hearts which have enlarged subsequent to cyclic nucleotide response modification, the role of cyclic nucleotides in regulating adaptive heart growth will be verified. Moreover, interventions capable of modifying adaptive heart growth will be identified.